tbuckley/cabot-search huggingface dataset:
AB0576 SERUM 25-HYDROXYVITAMIN D WAS CORRELATED WITH THE DISEASE ACTIVITY IN TAKAYASU’S ARTERITIS
Authors: H. Liao
Journal: Annals of the Rheumatic Diseases (2022)

Background 25-Hydroxyvitamin D [25(OH)D] deficiency has been linked to autoimmune disease. However, the relationship between 25(OH)D and Takayasu’s arteritis (TAK) disease activity remains largely unknown[1] Objectives This study aimed to investigate the association between serum 25(OH)D and disease activity in TAK patients. Methods A total of 117 patients with TAK (TAK group) and 75 healthy people (control group) were enrolled in our study. Fifty-nine of the patients were re-evaluated after six months of therapy. The serum 25(OH)D levels were compared between the groups. The correlations between the 25(OH)D levels and TAK disease activity were analyzed. Results The serum 25(OH)D levels were markedly lower in the TAK patients than those in the healthy subjects [(12.16±4.9) μg/L vs (21.97±8.33) μg/L] (P&lt;0.001). Serum 25(OH)D in all TAK patients was negatively correlated with IL-6 (r=-0.214, P=0.035). The serum 25(OH)D levels in the TAK patients were significantly higher after six months of therapy with glucocorticoid and immunosuppressive agents than those at baseline [(12.16±4.9) μg/L vs (18.01±7.32) μg/L] (P&lt;0.001). Finally, we showed that elevated changes in the 25(OH)D levels before and after treatment were positively correlated with reduced changes in the NIH, ITAS2010 and ITAS-A scores (r=0.490, P&lt;0.001; r=0.496, P&lt;0.001; and r=0.306, P=0.018, respectively). Conclusion The serum 25(OH)D levels were significantly downregulated. The changes in 25(OH)D were positively correlated with changes in disease activity. References [1]Keser G, Aksu K, Direskeneli H. Discrepancies between vascular and systemic inflammation in large vessel vasculitis: an important problem revisited. Rheumatology (Oxford) 2017. Disclosure of Interests None declared
POS1326 PIMS THROUGH THE WAVES OF COVID 19: DATA FROM THE JIR COHORT
Authors: R. Kechiche, A. Schvartz, F. Bajolle, S. Poignant, R. Basmaci, C. Pajot, U. Meinzer, L. Morin, V. Lambert, P. Dusser, N. Matsa, M. Hofer, I. Koné-Paut, G. Caroline
Journal: Annals of the Rheumatic Diseases (2022)

Background Paediatric inflammatory multisystem Syndrome (PIMS) is a new systemic inflammatory disease linked to SARS-CoV2 that affects children. It was first reported in may 2020 [1-2] . Objectives The objectives of this study were to describe patients with PIMS through the international JIR cohort registry and to compare the different profiles and treatments of these patients over the different waves. Methods Study patients with international PIMS criteria were included from March 2020 to June 2021. Patients were identified in the JIR cohort, an international registry collecting demographic, clinical and paraclinical data on patients with pediatric inflammatory diseases. Two groups were distinguished: from March 2020 to July 2020 for patients in the first wave, from July 2020 to June 2021 for patients in the 2nd and 3rd waves. These two groups were compared using a Fischer test for categorical data and a Mann-Whitney test for quantitative data Results 136 patients meeting the PIMS criteria were included (64 patients in the 1st wave, 72 patients after). Patients had less frequent myocarditis (51 patients in wave 1 vs. 36 patients after, p=0,0003) and respiratory distress (34 patients vs 10 patients, p&lt;0,0001). Corticosteroids were used more frequently in the second wave (32 patients in wave 1 vs. 67 patients after July 2020, p&lt;0,0001). Intravenous immunoglobulins were used as much over the waves (58 patients in wave 1 vs 68 patients after, p=0.5). Antibiotics were less used since the second wave (53 patients received antibiotics before July 2020 vs 11 after, p&lt;0,0001). The duration of hospitalization decreased significantly (p&lt;0,0001) with a median duration of 9 days during the first wave (interquartile range, 7-12) and 7 days (interquartile range, 5-10) after the first wave. Conclusion There was a decrease in the number of complications of PIMS, particularly cardiac and respiratory complications, and a decrease in the length of hospitalization over time. The treatment of PIMS has also evolved, with a clear increase in the use of corticosteroids and a decrease in the use of antibiotics. References [1]Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P (2020) Hyperinflammatory shock in children during COVID-19 pandemic. Lancet 395:1607–1608. [2]Verdoni L, Mazza A, Gervasoni A, Martelli L, Ruggeri M, Ciuffreda M, Bonanomi E, D’Antiga L (2020) An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet. 395:1771–1778 Acknowledgements Acknowldgements to the French Covid-19 Paediatric Inflammation Consortium. Disclosure of Interests None declared
AB0588 GIANT CELL ARTERITIS: DO DIFFERENT PHENOTYPES OF PRESENTATION MEAN DIFFERENT CLINICAL ENTITIES?
Authors: N. Italiano, F. Di Cianni, E. Elefante, F. Ferro, P. A. Erba, R. Talarico, M. Mosca
Journal: Annals of the Rheumatic Diseases (2022)

Background Giant cell arteritis (GCA) represents the most common primary vasculitis of the elderly, affecting large and medium-sized arterial vessels. GCA often also involves the aorta and its major branches and may lead to aortic aneurysm/dissection as well as large artery stenoses; it seems that unrecognized extra-cranial involvement may be even more common. Objectives The primary aim of this study was to explore the different clinical entities in a large cohort of patients with GCA; a secondary aim was to evaluate long-term outcome of GCA patients with at least 5 years of follow-up. Methods A cohort of 278 GCA patients (54 males and 224 females, mean ± SD age 75 ± 6 years) were retrospectively studied. Clinical symptoms at disease onset and during the follow-up, time delay until diagnosis, as well as laboratory findings at the time of diagnosis and therapeutic approach were retrospective evaluated. In order to characterize the different clinical phenotypes, overall clinical symptoms were grouped for macro-area (cranial versus systemic). Moreover, long-term outcomes in patients with a minimum follow-up of 3 years were evaluated. A disease flare was defined as the presence of any further clinical manifestation compatible with the clinical spectrum of GCA and an increase of ESR ≥ 30 mm/hour, not otherwise justifiable, that required higher doses or new introduction of glucocorticoids (GC) therapy and/or the introduction of steroid sparing treatments (e.g. tocilizumab, methotrexate). Results The most frequent clinical manifestations presented at the onset included: constitutional symptoms 69%, new onset headache and/or scalp pain 64%, jaw claudicatio 32%, vision loss 30%, abnormal temporal artery on examination 19%, neuropsychiatric symptoms 17%, cough not otherwise justifiable 7%, cerebrovascular accidents 6% and hearing loss 3%. Irreversible (mono- or bilateral) blindness was reported in 7% of patients, mainly due to a latency period between onset and treatment of ≥ 3 months. Temporal artery biopsy was performed in 171 patients, resulting positive in 72%. Globally, about 38% of subjects (was characterized by a clinical profile compatible with extra-cranial GCA. In all cases, extra-cranial involvement was confirmed by (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Moreover, patients who presented symptoms compatible with large-vessel involvement were characterized by a more relapsing course compared with patients with cranial involvement GCA profile (both in terms of dose of corticosteroids and use of steroid-sparing agents). Conclusion According to the literature data, different phenotypes of GCA exist and they may probably represent different clinical entities, also in terms of prognosis and therapeutic approach. This is particularly crucial in order to plan a tailored therapy and prevent disease damage in the short and long-term follow-up. Disclosure of Interests None declared
AB1301 DETERMINING THE RELATIONSHIP BETWEEN SERUM INTERLEUKIN 33 LEVELS AND CLINICAL FEATURES OF THE DISEASE IN PATIENTS WITH FAMILIAL MEDITERRANEAN FEVER
Authors: A. Demirezen, A. Avanoglu Guler, H. Karadeniz, D. Yildirim, H. Küçük, M. Kavutcu, M. A. Ozturk, A. Tufan
Journal: Annals of the Rheumatic Diseases (2022)

Background Familial Mediterranean Fever (FMF) is an autoinflammatory disease characterized by recurrent fever, serositis, arthritis and erysipelas-like erythema caused by mutations over activating caspase-1. As Interleukin (IL)-1 beta, IL-33 is a nuclear cytokine from IL-1 family which is activated by caspase-1. IL-33 is known to take part in pathogenesis of several rheumatic diseases. Objectives The aim of this research is determining the relationship between serum IL-33 levels and clinical features of the disease in patients with FMF disease. Methods The research involved 54 FMF patients and 29 healthy volunteers. Serum IL-33 levels were evaluated in both patients and healthy individuals, and its relationship between clinical and laboratory features of FMF. Results 28 out of 54 patients (%51.8) had favorable response to colchicine while 26 patients (%48.2) had colchicine resistant disease. FMF patients had lower IL-33 levels compared to healthy control group (p= 0.06). There were no difference between colchicine responsive and resistant patients (p=0.12) and no association was found between clinical features and serum IL-33 levels. Additionally, IL-33 did not correlated with C-reactive protein and disease activity assessed by autoinflammatory disease activity index. Conclusion No association was found between serum IL-33 levels and FMF disease features and laboratory findings. This may be due to the small size of our patient group, the involvement of IL-33 in tissue homeostasis as well as inflammation, and the use of higher doses of colchicine in the resistant disease group than in the remission group. Additional research is needed to determine IL-33’s role in FMF pathogenesis and its relationship with clinical and laboratory features. References [1]Ozdogan, H. and S. Ugurlu, Familial Mediterranean Fever. Presse Med, 2019. 48(1 Pt 2): p. e61-e76. [2]Cayrol, C. and J.P. Girard, Interleukin-33 (IL-33): A nuclear cytokine from the IL-1 family. Immunol Rev, 2018. 281(1): p. 154-168. [3]Duan, L., et al., The role of IL-33 in rheumatic diseases. Clin Dev Immunol, 2013. 2013: p. 924363. Acknowledgements None of the authors obtained any financial support. Disclosure of Interests None declared
AB0845 IMPORTANCE OF WEIGHT MANAGEMENT ON ENDOTHELIAL FUNCTION IN SPONDYLOARTHRITIS
Authors: A. Ben Tekaya, E. Hannech, A. Fendri, S. Boukriba, O. Saidane, S. Bouden, R. Leila, R. Tekaya, I. Mahmoud, H. Mizouni, L. Abdelmoula
Journal: Annals of the Rheumatic Diseases (2022)

Background Subclinical atherosclerosis is not rare in spndyloarthritis (SpA) patients. Endothelial dysfunction is the first step of atherosclerosis process. Obesity is a major traditional cardiovascular risk factor. Objectives The purpose of our study was to determine the association of anthropometric measures with endothelial dysfunction in non-obese SpA patients. Methods This was a prospective study conducted over 12 months and including 47 SpA free cardiovascular disease patients and aged less than 50 years. The following anthropometric parameters were collected for each patient: weight, height, Body Mass Index (BMI), hip and waist circumferences. Endothelial dysfunction was assessed by the ultrasound evaluation of the Flow Mediated Dilatation (FMD). Results There were 14 female (28.8%) and 33 male (70.2%). The median age was 36 years (IQR; 18-50). The median disease duration was 11 years (IQR; 1-32). The median weight, height and BMI were 69 (IQR; 43-95), 170 cm (IQR; 144-193) and 24.5 kg/m 2 (IQR; 16.33 - 29.41), respectively. Overweight (BMI: 25-29 kg/m 2 ) was noted in 40% of patients. The median hip and waist circumferences were respectively 100 cm (IQR; 84-116) and 88 cm (IQR; 70-114). Median FMD was 18.18% (IQR; 12.8-23.1). We didn’t found correlation between anthropometric parameters and FMD: weight (p=0.225; r=-0.180); height (p=0.273; r=-0.163), BMI (p=0.437; r=-0.116); waist circumference (p=0.22; r=-0.182) and hip circumferences (p=0.142; r=-0.217). Conclusion Our study showed that anthropometric parameters do not influence endothelial function in non-obese and young SpA patients. This highlights the importance of weight management and maintaining a healthy weight in SpA patients. Disclosure of Interests None declared
AB0755 Hip denervation and intra-articular hydration in axial spondyloarthritis patients with hip damage
Authors: A. Elsaman, A. Khalifa, A. Maaty
Journal: Annals of the Rheumatic Diseases (2022)

Background The hip joint is frequently affected in axial spondyloarhritis (SpA) of the adults with destructive effect in untreated patients. About 35% of axial SpA patients had either unilateral or bilateral hip arthritis. Destruction is more common with early-onset, active disease, or enthesitis [1, 2]. Objectives The aim of this study is to evaluate the effect of hip denervation (HD) and intra-articular hydration (IAH) on pain, function score, hip mobility scores in a cohort of axial SpA patients with grade 3 and 4 hip BASRI score. Methods We enrolled 40 patients who fulfilled ASAS criteria for axial SpA. All had hip involvement with grade 3 or 4 BASRI score at baseline. They were divided into 4 groups; group one received placebo, group 2 HD, group 3 IAH, and group 4 received HD and IAH. They all were assessed at baseline and after 4 weeks and 12 weeks. Outcome measures included; VAS, semi-quantitative scores of tenderness for the hip, range of motion, and Harris functional hip score (HHS). Results A significant improvement of VAS pain, tenderness score, ROM, HHS were detected in group 4 versus other groups (p &lt; 0.05). Group 2 had significantly lower scores of tenderness and pain compared to group 3 (p &lt; 0.05). In contrast, the patients of group 3 show better ROM and HHS than the patients of group 2 (p &lt; 0.05). At 4- and 12-week, all therapeutic groups (2, 3, and 4) show considerable improvement in comparison to placebo (group 1) (p &lt; 0.05). Conclusion HD and IAH can improve pain and function in damaged hip of axial SpA patients, especially when concurrently used. References [1]Han, Q., et al., A Comprehensive Assessment of Hip Damage in Ankylosing Spondylitis, Especially Early Features. Frontiers in Immunology, 2021. 12: p. 880. [2]Elsaman, A., A. Hamed, and A. Radwan, Ultrasound-guided epidural block in axial spondyloarthritis patients with limited spine mobility: a randomized controlled trial. The Korean journal of pain, 2021. 34(1): p. 114. Disclosure of Interests None declared
Duplication of Horizontally Acquired GH5_2 Enzymes Played a Central Role in the Evolution of Longhorned Beetles
Authors: Na Ra Shin, Daniel Doucet, Yannick Pauchet
Journal: Molecular Biology and Evolution (2022)

Abstract The rise of functional diversity through gene duplication contributed to the adaption of organisms to various environments. Here we investigate the evolution of putative cellulases of the subfamily 2 of glycoside hydrolase family 5 (GH5_2) in the Cerambycidae (longhorned beetles), a megadiverse assemblage of mostly xylophagous beetles. Cerambycidae originally acquired GH5_2 from a bacterial donor through horizontal gene transfer (HGT), and extant species harbor multiple copies that arose from gene duplication. We ask how these digestive enzymes contributed to the ability of these beetles to feed on wood. We analyzed 113 GH5_2, including the functional characterization of 52 of them, derived from 25 species covering most subfamilies of Cerambycidae. Ancestral gene duplications led to five well-defined groups with distinct substrate specificity, allowing these beetles to break down, in addition to cellulose, polysaccharides that are abundant in plant cell walls (PCWs), namely, xyloglucan, xylan, and mannans. Resurrecting the ancestral enzyme originally acquired by HGT, we show it was a cellulase that was able to break down glucomannan and xylan. Finally, recent gene duplications further expanded the catalytic repertoire of cerambycid GH5_2, giving rise to enzymes that favor transglycosylation over hydrolysis. We suggest that HGT and gene duplication, which shaped the evolution of GH5_2, played a central role in the ability of cerambycid beetles to use a PCW-rich diet and may have contributed to their successful radiation.
Reengineering Ponatinib to Minimize Cardiovascular Toxicity
Authors: Anna P. Hnatiuk, Arne A.N. Bruyneel, Dhanir Tailor, Mallesh Pandrala, Arpit Dheeraj, Wenqi Li, Ricardo Serrano, Dries A.M. Feyen, Michelle M. Vu, Prashila Amatya, Saloni Gupta, Yusuke Nakauchi, Isabel Morgado, Volker Wiebking, Ronglih Liao, Matthew H. Porteus, Ravindra Majeti, Sanjay V. Malhotra, Mark Mercola
Journal: Cancer Research (2022)

Abstract Small molecule tyrosine kinase inhibitors (TKI) have revolutionized cancer treatment and greatly improved patient survival. However, life-threatening cardiotoxicity of many TKIs has become a major concern. Ponatinib (ICLUSIG) was developed as an inhibitor of the BCR-ABL oncogene and is among the most cardiotoxic of TKIs. Consequently, use of ponatinib is restricted to the treatment of tumors carrying T315I-mutated BCR-ABL, which occurs in chronic myeloid leukemia (CML) and confers resistance to first- and second-generation inhibitors such as imatinib and nilotinib. Through parallel screening of cardiovascular toxicity and antitumor efficacy assays, we engineered safer analogs of ponatinib that retained potency against T315I BCR-ABL kinase activity and suppressed T315I mutant CML tumor growth. The new compounds were substantially less toxic in human cardiac vasculogenesis and cardiomyocyte contractility assays in vitro. The compounds showed a larger therapeutic window in vivo, leading to regression of human T315I mutant CML xenografts without cardiotoxicity. Comparison of the kinase inhibition profiles of ponatinib and the new compounds suggested that ponatinib cardiotoxicity is mediated by a few kinases, some of which were previously unassociated with cardiovascular disease. Overall, the study develops an approach using complex phenotypic assays to reduce the high risk of cardiovascular toxicity that is prevalent among small molecule oncology therapeutics. Significance: Newly developed ponatinib analogs retain antitumor efficacy but elicit significantly decreased cardiotoxicity, representing a therapeutic opportunity for safer CML treatment.
AB0915 GUSELKUMAB REAL WORD DATA: EFFICACY AND SAFETY IN A COHORT OF 69 PATIENTS WITH PSORIATIC ARTHRITIS
Authors: M. S. Chimenti, M. Galluzzo, M. Talamonti, A. Campanati, C. Bonifati, P. Bruni, G. Caldarola, A. Carpentieri, A. Chiricozzi, C. De Simone, F. Diotallevi, M. Esposito, C. Fiorella, D. Graceffa, F. Loconsole, K. Hansel, C. Mugheddu, M. Papini, A. Richetta, A. Bergamini, M. M. Luchetti, L. Atzori, K. Peris, A. Offidani, L. Stingeni, L. Bianchi
Journal: Annals of the Rheumatic Diseases (2022)

Background Psoriasis (PSO) is a systemic immune-mediated disorder, characterized by inflammation skin and joint manifestations: it is known that up to 30% of PsO patients develop PsA. PsO and PsA share common etiopathogenetic pathways, as IL-23/IL-17 axis. In Italy, Guselkumab (GUS), a selective IL-23 inhibitor, was approved in 2018 for the treatment of PsO, and recently it was also approved for PsA therapy. Today, there are few “real-world” studies regarding the use of GUS in PsA patients. Objectives A multicenter Italian study group of dermatologists and rheumatologists aimed at evaluate GUS efficacy and safety in patients with concomitant PsO and PsA in real word setting on both skin and joint domains. Methods An observational retrospective, multicentric study was performed in 69 PsO patients with a confirmed diagnosis of moderate to severe PsA. PASI and DLQI were used for the evaluation of skin response, and the number swollen/tender joints, presence or absence of dactylitis or enthesitis or axial involvement and painVAS were evaluated for the articular and periarticular efficacy. These analyses were performed at baseline T0 (beginning of the therapy), T1 (12 weeks) and T2 (24 weeks). Results 38/69 patients (55,1%) presented oligoarthritis, 31/69 (44,9%) showed polyarthritis, none of the patients had enthesitis or axial involvement. Moreover, co-morbidities were diagnosed: hypertension (52,2%), hypercholesterolemia (34,8%), Hypertriglyceridemia (29%), diabetes (24,6%), obesity (23,2%), HIV-positive (20,3%), psychiatric disorders (17,4%), cardiopathies (15,9%), inflammatory bowel disease (7,3%), Latent Tubercolosis (4,4%), Chronic B-Hepatitis (2,9%), Chronic C-Hepatitis (1,5%). In all these patients, skin and joint responses were evaluated at week 12 and week 24. Concerning skin efficacy, PASI 90 was achieved at week 24. Concerning Joint response: painVAS progressively improved till T2, tender joint count decreased in patients with oligo and polyarthritis at T1 and maintained at T2, while swollen joint count decreased in polyarthritis patients at T1 and maintained at T2. In oligo-arthritis patients, this parameter was not improved. The number of dactylitis did not decrease during the period of study (see Table 1). No safety concerns were reported in this population. Conclusion Efficacy and safety of GUS was confirmed in this study group of PsO patients with concomitant PsA and several comorbidities in a real-life setting. Disclosure of Interests None declared